The pathogenesis of widespread pain and fibromyalgia (FM) is unknown. Altered responses from the hypothalamus-pituitary-adrenal axis, sympathetic nervous system and muscular system have been suggested as being of importance. The present study was undertaken to determine: (i) whether the sympathoadrenal response to repetitive isometric contractions until exhaustion is altered in patients with FM, and (ii) whether sympathoadrenal responses are associated with muscle fatigue and pain during exercise. Nineteen women with FM, and 19 healthy women matched for age, smoking and self-reported physical activity, participated. Maximal voluntary contraction (MVC), repetitive isometric contractions (6s contraction and 4s resting phases) were performed with both quadriceps muscles at 30% of MVC until exhaustion. Muscle activity was recorded from the quadriceps muscles by surface electromyography (EMG). Plasma adrenalin (Adr), noradrenalin (NAdr) and cortisol were measured and perceived exertion and pain reported during exercise. Attenuated Adr responses (p<0.001) with normal plasma NAdr and cortisol (p>0.19) responses were found during exercise in the FM group compared with the control group. Significantly higher EMG amplitude (%EMG(max)) during the contraction phases (p=0.001) was found in the FM than in the control group. Perceived exertion and pain responses to exercise were higher in the FM group than in the controls (p<0.001), without relationship to the sympathoadrenal responses. In conclusion; the exercise was perceived as being more painful and strenuous in the FM group. Muscle performance was altered with increased muscle activity during the exercise. Women with FM showed an attenuated Adr response to repetitive isometric exercise.